The physiological function of lipoprotein particles is to transport lipids and lipid soluble material in the bloodstream to and from the liver. Low density lipoprotein (LDL) is the main transporter of cholesterol to the peripheral tissues, while excess tissue cholesterol is returned to the liver by reverse cholesterol transport mediated by HDL. In parallel with the transport functions, high LDL cholesterol is associated with elevated risk of cardiovascular disease, while high HDL cholesterol appears to be protective.
Along with the native lipids, LDL and HDL particles are known to contain products of lipid peroxidation. Oxidized LDL lipids may be derived from endogenous lipid peroxidation reactions, or directly from peroxidized dietary lipids. Oxidized HDL lipids, in turn, may be received directly from LDL, or from endogenous lipid peroxidation. Products of lipid peroxidation are toxic, and in many ways involved in the development of atherosclerosis. They are directly linked with macrophage accumulation, regulation of macrophage activity and foam cell formation in vessel wall, and with activation of atherosclerosis-related gene groups1.
Peroxidized lipids are also the cause of intracellular oxidative stress and inflammatory response: Oxidative stress results in activation of nuclear factor κB (NFκB), leading to production of cytokines and other mediators of the inflammatory response. These will then elicit in the liver the synthesis of acute phase proteins, which are the common indicators of inflammatory response (FIG. 1). Interestingly, experimental studies seem to indicate that cholesteryl ester hydroperoxides in HDL can be taken up by the liver2. In addition to the central role in lipid metabolism, recent studies have shown that HDL can have anti-inflammatory effects by counteracting the proinflammatory effect of oxidized LDL3. The anti-inflammatory effect of HDL has been attributed to attenuation of the NFκB activation by oxidants3.
Oxidation of HDL can be assayed either in lipid or apolipoprotein moieties of HDL. Various publications disclose measurement of the levels of oxidised apolipoprotein A-I moiety of HDL4-6, and discuss the meaning of said levels in certain diseases. However, determination of the oxidation of the lipid moiety of HDL has not been disclosed or discussed earlier.